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Biomedical subjects

D Le Bars

Publications and source records attributed to D Le Bars.

At least 145 records · Page 8Linked to original sources
PubMed1986

Lesions of dorsolateral funiculi (DLF) do not affect the depressive effects of systemic morphine upon dorsal horn convergent neuronal activities related to pain in the rat.

It has been shown that morphine could interact with supraspinal inhibitory controls which modulate the transmission of nociceptive messages at the spinal level. However, the way in which such interactions occur is still a subject of controversy. Based on behavioural experiments, it has been proposed that systemic morphine increases descending inhibitory controls travelling via the dorsolateral funiculus (DLF). To directly test this hypothesis from an electrophysiological standpoint, we have investigated the effects of morphine upon C-fibre responses of dorsal horn convergent neurones in rats with bilateral lesions of the DLF. Previous studies by our group have shown that 6 mg/kg morphine chlorhydrate was the intravenous mean effective dose for depressing by 50% (ED50) the C-fibre evoked responses of convergent neurones recorded at the lumbar level. In the present work, the effects of 6 mg/kg morphine were investigated under identical experimental conditions, except that a bilateral destruction of the dorsolateral funiculus (DLF) was performed previously. These lesions did not change the mean C-fibre evoked responses. Following morphine administration, the C-fibre evoked responses were depressed by 47.1 +/- 10.1% (n = 13) and reversal of these effects by naloxone was always observed. The A-fibre evoked responses, concurrently recorded, were not modified by the drug. As the depressive effects observed with this dose of morphine appear to be essentially of the same magnitude as those previously found in the intact or spinal preparations, we conclude that the DLF is not involved in the depressive effects of systemic morphine on dorsal horn convergent neurones.

Animals↗
PubMed1986

The response to viscero-peritoneal nociceptive stimuli is reduced in experimental arthritic rats.

Reciprocal inhibitory influences of heterotopic nociceptive stimuli have been known for centuries (counter-irritation phenomena). To assess whether such phenomena could be measured objectively in a chronic pain model, we have investigated the writhing behaviour induced by a viscero-peritoneal nociceptive stimulus (i.p. acetic acid) in arthritic rats. The latter was induced by s.c. injection of mycobacterium butyricum suspended in oil into the base of the tail and experiments carried out at various (1-9 weeks) post-inoculation periods. To assess the arthritis-induced hyperaesthesia, the threshold for struggle triggered by a calibrated pressure applied on an inflamed hindpaw (Randall-Selitto test) was measured before each experiment. A clear relationship was observed between the two parameters during the evolution of the disease. In the most severe phase (2nd to 5th week post-inoculation), when arthritis-induced hyperaesthesia was most pronounced (50% reduction of the threshold for struggle), writhing behaviour was strongly reduced (80%). At that time, writhing behaviour was enhanced by naloxone (0.4 mg/kg i.v.). In the following period (5-9 weeks), the progressive decrease of hyperaesthesia was correlated with a recovery of the writhing behaviour. We conclude that in this chronic pain model, the behavioral reaction to a viscero-peritoneal nociceptive stimulus is impaired. Endogenous opioid systems could be involved in this phenomenon. Such heterotopic inhibitory processes could be relevant to some paradoxical clinical observations such as the masking of a pain by the experience of pain at another locus.

Abdomen↗
PubMed1986

Ascending pathways in the spinal cord involved in triggering of diffuse noxious inhibitory controls in the rat.

Recordings were made from convergent neurons in trigeminal nucleus caudalis of the rat. These neurons were activated by both innocuous and noxious mechanical stimuli applied to their excitatory receptive fields located on the ipsilateral part of the muzzle. Transcutaneous application of suprathreshold 2-ms square-wave electrical stimuli to the center of the excitatory field resulted in responses to C-fiber activation being observed (mean latencies 63.6 +/- 5.5 ms). This type of response was inhibited by applying noxious conditioning stimuli to heterotopic body areas, namely immersing either the left or right hindpaw in a 52 degrees C water bath. A virtually total block of the response was observed during the application of the noxious conditioning stimulus, and this was followed by long-lasting poststimulus effects. Such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC) (39, 40). The effects on these inhibitions of various transverse lesions of the cervical spinal cord were investigated in acute experiments; tests were performed before and at least 30 min after the spinal section. While the unconditioned C-fiber responses were unaltered, the inhibitory processes could be impaired by the cervical lesions, although these effects depended on the part of the cervical cord destroyed and the side of application of the conditioning stimulus. Lesioning dorsal, dorsolateral, and ventromedial parts of the cervical cord was found not to affect inhibitory processes triggered from either hindpaw. The overlapping of the regions of these ineffective lesions revealed that two remaining regions were not destroyed, that is, the left and right ventrolateral quadrants. In experiments where the left anterolateral quadrant was affected by the surgical procedure the inhibition triggered from the right hindpaw was strongly reduced, whereas that elicited by left hindpaw stimulation was not diminished. The loss of inhibitory effects was characterized by a complete disappearance of poststimulus effects, whereas inhibition observed during the application of the noxious thermal conditioning stimulus was only partially, albeit very significantly, blocked. To ascertain further the mainly crossed nature of the pathways responsible for the heterotopic inhibitory processes, the effects of lumbar commissurotomy were investigated. Again the unconditioned C-fiber responses were unaltered by this procedure, whereas the inhibitory processes, whether triggered from the left or right hindpaw, were strongly depressed in all the experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1986

Involvement of the dorsolateral funiculus in the descending spinal projections responsible for diffuse noxious inhibitory controls in the rat.

Recordings were made from convergent neurons in the lumbar dorsal horn of the spinal cord of the rat. These neurons were activated by both innocuous and noxious mechanical stimuli applied to their excitatory receptive fields located on the extremity of the hindpaw. Transcutaneous application of suprathreshold 2-ms square-wave electrical stimuli to the center of the excitatory field, resulted in responses to C-fiber activation being observed. This type of response was inhibited by applying a noxious thermal conditioning stimulus on the muzzle. The immersion of the muzzle in a 52 degrees C waterbath resulted in a strong reduction of the response during the application of the noxious conditioning stimulus and this was followed by long lasting poststimulus effects. Such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC). The effects on these inhibitions of lesions including the dorsolateral funiculus (DLF) were investigated in acute experiments: tests were performed before and at least 30 min after the DLF lesion. A lesion including the DLF ipsilateral to the neuron under study completely abolished the inhibitory processes triggered from the muzzle. Concomitantly, a facilitation of C-fiber responses was observed. Nevertheless, DNIC was still impaired even using a juxtathreshold current to elicit a weak C-fiber response. To ascertain further the main, if not entire, participation of the ipsilateral DLF in the descending projections responsible for the heterotopic inhibitory processes, the effects of a lesion of the contralateral DLF were investigated. Neither the inhibitory processes nor the unconditioned C-fiber responses were altered by this procedure. Again, a second lesion including the ipsilateral DLF induced a blockade of DNIC. It is concluded that the descending projections involved in the triggering of DNIC are mainly, if not entirely, confined to the DLF ipsilateral to the neuron under study. The contralateral DLF did not appear to play a role in these processes.

Animals↗
PubMed1986

[Reduction of the behavioral response to a viscero-peritoneal nociceptive stimulation during the development of experimental polyarthritis in the rat].

Writhing behaviour induced by a viscero-peritoneal nociceptive stimulus (i.p. acetic acid) has been investigated during the development of arthritis experimentally induced in rats by s. c. injection of Mycobacterium butyricum; experiments were carried out at various (1-9 weeks) post-inoculation periods. In the most severe phase (2-5 weeks post-inoculation), when arthritis-induced hyperaesthesia was most pronounced, writhing behaviour was strongly reduced (80%). In the following period, the progressive decrease of hyperaesthesia was contemporaneous with a recovery of the writhing behaviour. We conclude that, in this chronic pain model, the behavioural reaction to a viscero-peritoneal nociceptive stimulus is impaired. Such heterotopic inhibitory processes could be relevant to some paradoxical clinical observations such as the masking of a pain by the experience of pain at another locus (i. e. counter-irritation phenomenon).

Acetates↗
PubMed1986

Effects of kelatorphan and other peptidase inhibitors on the in vitro and in vivo release of methionine-enkephalin-like material from the rat spinal cord.

The effects of the novel mixed peptidase inhibitor, kelatorphan [N-(R)-3-(N-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)-L-alanine], were compared to those of a combination of the potent "enkephalinase" inhibitor thiorphan and the nonselective aminopeptidase inhibitor bestatin, on the catabolism of [3H]Met-enkephalin and on the release of endogenous Met-enkephalin by the rat spinal cord in vitro and in vivo. At 20 microM, kelatorphan almost prevented completely the degradation of exogenous [3H] Met-enkephalin by slices of the dorsal zone of the lumbar enlargement. Similarly, the addition of 20 microM kelatorphan to a [3H] Met-enkephalin-containing artificial cerebrospinal fluid superfusing the whole spinal cord of halothane-anesthetized rats efficiently protected the exogenous peptide from enzymatic degradation. In contrast, in the same in vitro and in vivo models, thiorphan (1 microM) or bestatin (20 microM) alone was inactive, and only their combination induced a significant protection of the exogenous peptide. In vitro and in vivo, kelatorphan (20 microM) increased markedly the spontaneous outflow of endogenous Met-enkephalin-like material as well as the peptide overflow due to K+-induced depolarization (in vitro and in vivo) or noxious stimulation (in vivo). Under similar conditions, thiorphan (1 microM) plus bestatin (20 microM) also enhanced the efflux of Met-enkephalin-like material, but generally to a lower extent than kelatorphan. Compared to thiorphan plus bestatin, kelatorphan exerts additional inhibitory effects on dipeptidylaminopeptidase activity and the present results could indicate that this enzyme also may be involved in the inactivation of extracellular Met-enkephalin at the spinal level in rats.

Animals↗
PubMed1985

Spontaneous and evoked release of methionine-enkephalin-like material from the rat spinal cord in vivo.

In vivo perfusion of the subarachnoid space with an artificial cerebrospinal fluid (CSF) in paralyzed halothane-anesthetized rats allowed the collection of methionine-enkephalin (Met-Enk)-like material (MELM) released from the spinal cord. Bio-Gel P2 chromatography and high-performance liquid chromatography showed that 65% of this material corresponded to authentic Met-Enk. Under resting conditions, about 1 pg of MELM per minute was regularly released for at least 3 h; for Met-Enk, this value corresponded to a fractional rate constant of 0.002% (i.e. tissue content of the pentapeptide which was released per minute from the whole spinal cord). Perfusion with K+-enriched (40-60 mM) CSF resulted in a marked enhancement (+ 150-200%) of spinal MELM release. Similarly, calibrated pinches of the muzzle and i.p. administration of acetic acid, two strong noxious stimuli in awake animals, induced a significant increase (+ 75-150%) in spinal MELM release. In contrast, pinches applied to the tail did not enhance but instead slightly reduced (-35%) MELM release from the rat spinal cord. These data suggest that mechanisms other than segmental controls could be involved in the activation of spinal enkephalinergic neurons by some nociceptive stimuli.

Animals↗
PubMed1985

Failure of ES 52, a highly potent enkephalinase inhibitor, to affect nociceptive transmission by rat dorsal horn convergent neurones.

The effects of ES 52, a highly potent derivative of the enkephalinase (enkephalin-dipeptidylcarboxypeptidase) inhibitor thiorphan, were studied on nociceptive activities of dorsal horn convergent neurones in the anaesthetized rat. Neither the C-fibre component of the responses elicited by supramaximal electrical stimulation of the hindpaw excitatory receptive fields nor diffuse noxious inhibitory controls triggered by immersion of the tail in 46-48 degrees C waterbaths, were affected by ES 52. Thus we conclude that, in our experimental conditions, modulations of the transmission of nociceptive messages at the spinal level are not greatly modified by specifically blocking the degradation of enkephalins. If a major role for enkephalinase (vs aminopeptidase) in the catabolism of enkephalins at the spinal level can be confirmed, then comparison of the present data with our previous results obtained using the opioid antagonist naloxone, might suggest a predominant role for proenkephalin B products (i.e. dynorphins and/or alpha-neo-endorphin) in modulating nociceptive transmission in the spinal cord.

Amino Acids, Sulfur↗
PubMed1985

The encoding of thermal stimuli applied to the tail of the rat by lowering the excitability of trigeminal convergent neurones.

Recordings were made from convergent neurones in the nucleus caudalis of the trigeminal complex. They could be excited by both innocuous and noxious stimuli applied to their excitatory receptive field located on the ipsilateral part of the muzzle. The responses to A- and C-fibre activation induced by supramaximal transcutaneous electrical stimulation of their receptive fields were conditioned by thermal stimuli applied to the tail, and the relationship between the conditioning temperatures and their ability to induce inhibitions of the evoked discharges of convergent neurones were investigated. During sequences of repetitive stimulation, the posterior two-thirds of the tail were immersed in a waterbath at various temperatures (36-52 degrees C) and the resultant inhibitions of responses were calculated. The threshold for obtaining an inhibitory effect ranged between 40 and 44 degrees C. Above this level, there was a highly significant correlation between the conditioning temperature and the degree of inhibition, which was very strong for the highest temperature (i.e. for 52 degrees C: 54.4 +/- 7.3 and 92.3 +/- 3.7% inhibitions being obtained for A- and C-fibre-evoked responses respectively); such a correlation concerned the inhibitions observed both during immersion of the tail and after the removal of the conditioning stimuli. In further experiments, identical conditioning stimuli were tested upon responses of trigeminal convergent neurones to microelectrophoretic applications of an excitatory amino acid, DL-homocysteate, and very similar results were obtained: a threshold for inhibition in the 40-44 degrees C range and a significant correlation between the conditioning temperature and the degree of inhibition in the 44-52 degrees C range (52 degrees C giving inhibitions of 98.8 +/- 0.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1984

Diffuse noxious inhibitory controls (DNIC): evidence for post-synaptic inhibition of trigeminal nucleus caudalis convergent neurones.

Activity produced by direct microelectrophoretic application of glutamate onto 19 convergent neurones in trigeminal nucleus caudalis, was strongly depressed during and after the application of heterotopic noxious conditioning stimuli: noxious heat (52 degrees C) applied to the tail, noxious pinches applied to the tail or hindpaws and intraperitoneal injections of bradykinin produced mean reductions in activity of 80-90%. The same noxious conditioning stimuli had no effect on the activities of any of 5 noxious-only or 5-non-noxious-only neurones. These effects were similar to those previously reported to influence peripherally evoked activities of nucleus caudalis convergent neurones and which have been termed diffuse noxious inhibitory controls (DNIC). It is therefore proposed that DNIC act on nucleus caudalis convergent neurones by a final post-synaptic inhibitory mechanism involving hyperpolarization of the neuronal membrane. Consistent with this hypothesis, it was also found that the noxious conditioning stimuli could restore firing of convergent neurones which had been excessively depolarised by large doses of glutamate.

Animals↗
PubMed1984

Evidence that diffuse noxious inhibitory controls (DNIC) are medicated by a final post-synaptic inhibitory mechanism.

Nineteen convergent neurones, 19 'non-noxious only' neurones and 13 'proprioceptive' neurones all with peripheral excitatory receptive fields on the ipsilateral hindpaw, were recorded in the lumbar dorsal horn of non-spinalized, anaesthetized rats. These neurones were all excited by the electrophoretic application of glutamate; using 20 s applications of appropriate electrophoretic currents, almost identical levels of activity (around 30 spikes/s) were produced for each of the 3 types of neurones. The application of heterotopic noxious stimuli resulted in strong inhibitions of the glutamate-evoked activity of the convergent neurones. During the application of noxious heat (52 degrees C) to the tail and noxious pinches to the tail, contralateral hindpaw and muzzle, the glutamate-evoked activity was depressed by 78%, 84%, 63% and 59%, respectively. It was also found that these inhibitions outlasted the period of conditioning stimulation by several minutes (post-effects). Twenty seconds after i.p. injection of bradykinin (20 micrograms) the glutamate-evoked activity was depressed by 56% and this effect also lasted for several minutes. The application of identical heterotopic noxious stimuli did not affect the glutamate-evoked activity of the 'non-noxious only' neurones or the 'proprioceptive' neurones. The application to convergent neurones, of doses of glutamate, which were very much larger than the threshold for firing, produced an intense discharge followed by a progressive decrease in spike amplitude and finally a blocking of the spike discharge. During such sequences, which are typical of excessive depolarization, the application of noxious conditioning stimuli (e.g pinch of the contralateral hindpaw or muzzle) resulted in recovery of the spike discharge. In several cases, this recovery long outlasted the period of conditioning noxious stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Increase in 5-HT synthesis in the dorsal part of the spinal cord, induced by a nociceptive stimulus: blockade by morphine.

The effects of a nociceptive peripheral stimulus and/or morphine upon endogenous tryptophan levels (TRP), specific activity of tryptophan (S.A. of TRP) and serotonin (5-HT) synthesis in the dorsal and ventral spinal cord, the brainstem and the forebrain were investigated in anaesthetized rats. Whereas endogenous TRP and S.A. of TRP were not found to be affected by any of the manipulations described below, 5-HT synthesis was markedly altered. The application of a prolonged and intense nociceptive electrical stimulus to the tail induced a rise in 5-HT synthesis which was dependent on the part of the CNS considered, with the dorsal cord being the most sensitive (25%), the ventral cord and the brainstem being effected to a lesser extent (14% and 16% respectively), and the forebrain not being affected significantly. By contrast, the application of a prolonged and innocuous electrical stimulus on the tail was not followed by any detectable changes in 5-HT synthesis. Morphine administration (1 mg/kg; i.v.) did not significantly alter 5-HT synthesis in the four CNS regions considered. Nevertheless, the same morphine dose did induce a highly significant (P less than 0.005) reduction in the increase in 5-HT synthesis induced by the nociceptive stimulus, both in the dorsal cord and in the brainstem. Such an effect was not seen in the ventral cord. The specificity of these morphine effects was demonstrated by their naloxone reversibility; on the other hand, naloxone alone failed to modify the stimulus-induced increase in 5-HT synthesis seen in the dorsal cord and the brainstem. The results, particularly those concerning the dorsal cord, are discussed with reference to pain mechanisms and morphine analgesia. They suggest that peripheral nociceptive messages induce an increased activity in some bulbo-spinal 5-HT pathways and that a low dose of morphine can counteract such an effect. It is proposed that exogenous opiates exert a complex regulation of bulbo-spinal 5-HT pathways. Functional significances of these processes are discussed.

Afferent Pathways↗
PubMed1984

The heterotopic effects of visceral pain: behavioural and electrophysiological approaches in the rat.

The heterotopic effects of peritoneo-visceral pain were investigated in behavioural and electrophysiological experiments performed on rats. The intraperitoneal administration of acetic acid (i.p. AA), an algesic agent commonly used to induce writhing behaviour in rodents, was used as a conditioning stimulus in two parallel series of experiments involving 3 behavioural tests and recordings of dorsal horn convergent neurones. The responses to a nociceptive stimulus applied to the tail or paws were lowered by i.p. AA but these effects depended on the behavioural test used: in the tail-flick test, AA produced a transient low magnitude increase in latencies; the threshold for vocalization induced by electrical stimulation of the tail was clearly (25%) and sustainedly (full recovery taking up to 1 h) increased; the jump latency in hot plate was markedly increased (100% at 15 min). Intraperitoneal AA strongly depressed the C fibre evoked responses of coccygeal convergent neurones to suprathreshold transcutaneous electrical stimulation applied on their tail excitatory receptive fields. The time course of these inhibitory effects roughly paralleled the behavioural hypoalgesic effect observed in the vocalization test. These results are discussed with reference to diffuse noxious inhibitory controls (DNIC). Analogies with counter-irritation phenomena are emphasized.

Acetates↗
PubMed1984

Psychophysical and electrophysiological approaches to the pain-relieving effects of heterotopic nociceptive stimuli.

The nociceptive flexion reflex (RIII reflex) and the concurrent subjective pain score elicited by right sural nerve stimulation at random intensities were studied in 10 healthy volunteers. A close relationship was found between the recruitment curves of the reflex and the pain score as a function of stimulus intensity. As a consequence, the threshold of the RIII reflex (Tr) and of pain sensation (Tp) were found to be almost identical (mean: 9.8 and 11.3 mA, respectively). Similarly, the threshold for obtaining a maximal reflex response (Tmr) was found to be very close to that for intolerable pain (Tip): 33.5 and 35.1 mA, respectively. These four parameters were studied before and during the immersion of the left hand into a heated thermoregulated waterbath at various temperatures (from 40 to 47.5 degrees C). While nonnociceptive temperatures (40 to 44 degrees C) were without effect, higher conditioning temperatures induced an increase in the four thresholds. In addition, a highly significant linear relationship was observed between the increase in these thresholds and the intensity of the conditioning stimulus in the 44 to 47.5 degrees C range. These four parameters were also studied before and during three other nociceptive conditioning stimuli: immersion of the left hand into a 6 degrees C waterbath, 10 watts muscular exercise of the left hand performed under ischaemia and a painful (5.5 kg/cm2) pinch applied on the nasal septum. These three conditioning situations induced a very significant increase of the four thresholds considered in this study with the greatest being observed during nociceptive cold applied to the left hand. During all the conditioning situations, variations in Tr and Tp as well as in Tmr and Tip were found to be linearly related. This indicates a close relationship between the effects of the conditioning nociceptive stimuli on the reflex and the related pain sensation. These results suggest that the modulation of pain by heterotopic nociceptive stimuli can be explained at least in part by a depression in the transmission of nociceptive messages at the spinal level. They are discussed with reference to the counterirritation phenomena and common features with 'diffuse noxious inhibitory controls' (DNIC) are underlined.

Adult↗
PubMed1983

Depression of activities of dorsal horn convergent neurones by propriospinal mechanisms triggered by noxious inputs; comparison with diffuse noxious inhibitory controls (DNIC).

The ability of heterotopic noxious stimuli to inhibit the activity of dorsal horn convergent neurones was investigated in both intact anesthetized, and spinal unanesthetized rats. Forty-four convergent neurones in lumbar dorsal horn were recognized by their ability to respond to both noxious and non-noxious natural stimuli and by their characteristic responses corresponding to A- and C-fibre activity following electrical stimulation of their cutaneous excitatory receptive fields on the ipsilateral hindpaw. The application of a sustained pinch to the excitatory receptive field resulted in an initial phasic activation of the neurone, which adapted to a stable tonic level of activity (mean 31.8 +/- 2.2 spikes/s). The levels of activity produced in this fashion were not appreciably different between the two types of preparation. In the intact anesthetized rat, the tonic activity produced by the sustained pinch could be strongly depressed by noxious conditioning stimuli applied to various parts of the body for all 10 neurones studied: heating the tail or pinching the contralateral hindpaw, the tail or a forepaw during 30 s each resulted in comparable inhibitions which had mean values in the order of 80% and which were always marked by post-effects lasting for upwards of 30 s. These inhibitory effects have been called Diffuse Noxious Inhibitory Controls (DNIC). In the spinal unanesthetized rat, the tonic activity was depressed to some extent by the same conditioning stimuli, for only 16/34 neurones studied. By comparison with the intact animals these inhibitions were weak, adapted to base-line levels within 30 s and were more marked for conditioning stimuli applied to structures proximal (tail, contralateral hindpaw) to the excitatory receptive field than for stimuli applied more distally (forepaws). The differences between the inhibitions found in the intact and spinal preparations were subsequently confirmed in a series of experiments in which single convergent neurones were studied before and after the pharmacological blocking of the cervical spinal cord in anaesthetized rats. The results in the spinal preparations provide evidence for the existence of some propriospinal modulatory processes, triggered by the onset of noxious stimulation and acting on convergent neurones. These processes appear to be different from those mediating DNIC, which have been shown to involve supraspinal structures, to concern all convergent neurones, to be very potent and associated with long-lasting post-effects whether the conditioning noxious stimuli are applied to parts of the body proximal or distal to the excitatory receptive field.

Action Potentials↗